This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As many as 40% of Americans over the age of 85 may meet the criteria for clinical dementia, the most prevalent form of which is Alzheimer's Disease (AD) (US General Accounting Office, 1998). Understanding changes in brain function associated with early pre-clinical susceptibility to dementia in populations genetically at risk for AD can allow for study of intervention strategies before the onset of cognitive impairment. Recent studies using positron emission tomography (PET) have demonstrated that young (Reiman et al., 2004) and middle-aged (Reiman et al., 2001) carriers of the apolipoprotein E (APOE) ?4 allele, a genetic marker associated with increased risk of AD, exhibit functional abnormalities in the temporal and parietal regions of the brain in the absence of any clinical symptoms of dementia. Identification of such metabolic abnormalities in at-risk populations at such an early age allows for the study of prevention therapies to target the contributing processes prior to the onset of any cognitive decline. The evidence is now strong that physical exercise can protect and even enhance cognitive performance in aging populations (Colcombe &Kramer, 2003). Exercise has been shown influence brain function through upregulation of neurotrophic factors (Cotman &Engesser-Cesar, 2002), preservation of cortical structures (Colcombe et al., 2003), and maintained cerebral blood flow (Rogers, Meyer, &Mortel, 1990).